Cancer remains the second leading cause of death in the United States and it is estimated that over 500,000 individuals will die in the United States alone during 188. Historically, natural products or compounds modeled on them have found significant utility in the treatment of cancer and a number of marine-derived compounds are currently under clinical investigation. Advances in our understanding of neoplastic progression have provided new targets for intervention in cancer and may provide novel therapies with reduced side effects. In this proposal we seek to substantiate our hypothesis that marine natural products (MNPs) can be discovered which interact at these defined molecular targets and that these compounds, or compounds modeled upon them, will be useful in the treatment of cancer. The project will be carried out in collaboration with the Novartis Oncology Research group (NIBR), the Crews MNP group at UC Santa Cruz (UCSC) and the Gerwick group at Oregon State University (OSU). HBOI brings to the existing NPDDG a complementary set of extracts and expertise. The specific aims of the HBOI project are: 1. To provide a diverse and complementary library of extracts and enriched fractions to Project 1 (Novartis) for assay. These materials will be derived from marine invertebrates and fermentation of invertebrate- associated marine microorganisms. Focus will be on organisms derived from depths that those to typically accessible by acute (>200 feet of sea water). 2. To define whether fractionation and enrichment of the extracts through simple chromatographic procedures enhances the success rate for discovery of bioactive compounds by decreasing nuisance compounds, salts and complexity while increasing the concentration of the secondary metabolites assayed in the HTSs. 3. To rapidly deconvolute active extracts and fractions and define the structures of the active component(s). 4. To provide sufficient compound to the NIBR to allow for secondary biological testing and follow up.